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Vitamin A and Carotenoids

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Vitamin A: What is it?
Vitamin A plays an important role in vision, bone growth, reproduction, cell division and cell differentiation, which is the process by which a cell decides what it is going to become^{1, 4-7}. Vitamin A also maintains the surface linings of your eye and your respiratory, urinary, and intestinal tracts⁸. When those linings break down, bacteria can enter your body and cause infection⁸. Vitamin A helps your body regulate its immune system^{1, 4, 9}. The immune system helps prevent or fight off infections by making white blood cells that destroy harmful bacteria and viruses. Vitamin A may help lymphocytes, a type of white blood cell that fights infections, function more effectively. Vitamin A also may help prevent bacteria and viruses from entering your body by maintaining the integrity of skin and mucous membranes^{10, 11, 12}.

Vitamin A is a family of fat-soluble vitamins. Retinol is one of the most active, or usable, forms of vitamin A, and is found in animal foods such as liver and eggs. Retinol can be converted to retinal and retinoic acid, other active forms of the vitamin A family. Some plant foods contain orange pigments called provitamin A carotenoids that the liver can convert to retinol. Beta-carotene is a provitamin A carotenoid found in many foods^1-3. Lycopene, lutein, astaxanthin, and zeaxanthin are also carotenoids commonly found in food, but your body cannot convert them to vitamin A.

Some carotenoids, in addition to serving as a source of vitamin A, have been shown to function as antioxidants in laboratory tests. However, this role has not been consistently demonstrated in humans¹³. Antioxidants protect cells from free radicals, which are potentially damaging byproducts of the body's metabolism that may contribute to the development of some chronic diseases^{2, 14-16}.

What foods provide vitamin A?
Whole eggs, whole milk, and liver are among the few foods that naturally contain vitamin A. Vitamin A is present in the fat portion of whole milk, so it is not found in fat-free milk. Most fat-free milk and dried nonfat milk solids sold in the US are fortified with vitamin A¹⁷. There are many other fortified foods such as breakfast cereals that also provide vitamin A. The tables of selected food sources of vitamin A suggest animal sources of vitamin A and plant sources of provitamin A carotenoids¹⁸.

It is important for you to regularly eat foods that provide vitamin A or beta-carotene even though your body can store vitamin A in the liver¹. Stored vitamin A will help meet your needs when intake of provitamin A carotenoids or vitamin A is low^{19, 20.}

What is the Recommended Dietary Allowance for vitamin A for adults?
The Recommended Dietary Allowance (RDA) for vitamin A is the average daily dietary intake level that is sufficient to meet the nutrient requirements of nearly all (97-98%) healthy individuals in each life-stage and gender group¹³. The 1989 RDAs²¹ for vitamin A for adults and children are:

Results of the third National Health and Nutrition Examination survey (NHANES III 1988-91)²² suggested that the dietary intake of some Americans does not meet recommended vitamin A levels. The Continuing Survey of Food Intakes of Individuals (CSFII 1994)²³ suggested that diets of many Americans provide less than 75% of recommended vitamin A intake levels. These surveys highlight the importance of encouraging Americans to include dietary sources of vitamin A in their daily diets.

There is no separate RDA for beta-carotene or other carotenoids. The Institute of Medicine (IOM) report suggests that consuming 3 to 6 mg of beta-carotene daily will maintain plasma B-carotene blood levels in the range associated with a lower risk of chronic diseases¹³. This concentration can be achieved by a diet that provides five or more servings of fruits and vegetables per day.

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When can vitamin A deficiency occur?
Vitamin A deficiency rarely occurs in the United States, but it is still a major public health problem in the developing world. Vitamin A deficiency is most often associated with protein/calorie malnutrition and affects over 120 million children worldwide⁸. Vitamin A deficiency is also a leading cause of childhood blindness. In countries where immunization programs are not widespread and vitamin A deficiency is common, millions of children die each year from complications of infectious diseases such as measles⁸.

Signs of vitamin A deficiency include night blindness, dry skin, and decreased resistance to infections. In ancient Egypt it was known that night blindness could be cured after eating liver, which was later found to be a rich source of vitamin A¹. Vitamin A deficiency contributes to blindness by making the eye very dry, damaging the cornea of the eye (referred to as xerophthalmia), and promoting damage to the retina of the eye²⁴. Extremely dry skin, dry hair, sloughing off of skin, and broken fingernails are other common signs of vitamin A deficiency. Vitamin A deficiency also decreases resistance to infections^{1, 10}. When there is not enough vitamin A, cells lining the lung lose their ability to remove disease-causing microorganisms. This may contribute to the pneumonia associated with vitamin A deficiency⁹.

There is increased interest in subclinical forms of vitamin A deficiency, described as low storage levels of vitamin A that do not cause overt deficiency symptoms. This mild degree of vitamin A deficiency may increase children's risk of developing respiratory and diarrheal infections, decrease growth rate, slow bone development, and decrease likelihood of survival from serious illness^{8, 25, 26}.

Children living in the United States who are considered to be at increased risk for subclinical vitamin A deficiency include:

• toddlers and preschool age children
• children living at or below the poverty level
• children with inadequate health care or immunizations
• children living in areas with known nutritional deficiencies
• recent immigrants or refugees from developing countries with high incidence of vitamin A deficiency or measles, and
• children with diseases of the pancreas, liver, intestines, or with inadequate fat digestion/absorption⁸.

As a result of the worldwide significance of vitamin A deficiency in children, the World Health Organization (WHO) and the United Nations International Children's Emergency Fund (UNICEF) issued joint statements about vitamin A and children's health. Both agencies recommend vitamin A administration for all children diagnosed with measles in communities where vitamin A deficiency is a serious problem and where death from measles is greater than 1%. In 1994, the American Academy of Pediatrics recommended vitamin A supplementation for children 6 to 24 months of age hospitalized with measles and for hospitalized children older than 6 months who are considered to be at high-risk for subclinical vitamin A deficiency²⁷.

Who may need extra vitamin A to prevent a deficiency?
Children with low body stores of vitamin A who have measles may require vitamin A supplementation, as discussed above. Also, individuals with chronic fat malabsorption also poorly absorb vitamin A. Fat malabsorption can occur with cystic fibrosis, sprue, pancreatic disorders, and after stomach surgery. Healthy adults usually have a one-year reserve of vitamin A stored in their livers and should not be at risk of deficiency during periods of temporary or short term fat malabsorption. Long term problems absorbing fat, however, can result in deficiency and may require vitamin A supplementation⁸. Children may only have enough stores of vitamin A to last several weeks, so children with fat malabsorption may require immediate vitamin A supplementation⁸.

What is the association between vitamin A, beta carotene and cancer?
Surveys suggest an association between diets rich in beta-carotene and vitamin A and a lower risk of many types of cancer ^{1, 28}. There is evidence that higher intake of green and yellow vegetables or food sources of beta carotene and/or vitamin A decreased the risk of lung cancer²⁹. A number of studies have tested the role of beta-carotene supplements in cancer prevention³⁰. Unfortunately, recent intervention studies have not supported a protective role for beta carotene in cancer prevention. In a study of 29,000 men, incidence of lung cancer was greater in the group of smokers who took a daily supplement of beta carotene³¹. The Carotene and Retinol Efficacy Trial, a lung cancer chemoprevention trial that provided randomized subjects with supplements of beta carotene and vitamin A, was stopped after researchers discovered that subjects receiving beta carotene had a 46% higher risk of dying from lung cancer³². The IOM states that "Beta carotene supplements are not advisable for the general population", although they also state that this advice "does not pertain to the possible use of supplemental Beta carotene as a provitamin A source for the prevention of vitamin A deficiency in populations with inadequate vitamin A nutriture"¹³.

What is the health risk of too much vitamin A?
Hypervitaminosis A refers to high storage levels of vitamin A in the body that can lead to toxic symptoms. Toxicity can result in dry, itchy skin, headache, fatigue, hair loss, loss of appetite, vomiting, and liver damage. When toxic symptoms arise suddenly, which can happen after consuming very large amounts of vitamin A over a short period of time, signs of toxicity include dizziness, blurred vision, and muscular uncoordination^{6-8, 33, 34}.

Although hypervitaminosis A can occur when very large amounts of liver are regularly consumed, most cases of vitamin A toxicity result from an excess intake of vitamin A in supplements. A generally recognized safe upper limit of intake for vitamin A from diet and supplements is 1,600 to 2,000 RE (8,000 to 10,000 IU) per day^{33, 35}. The Institute of Medicine is currently reviewing the scientific literature on vitamin A. They are considering revising the RDAs and establishing an Upper Limit (UL) of safe intake for vitamin A.

Vitamin A toxicity also can cause severe birth defects. Women of childbearing age are advised to limit their total daily intake of vitamin A (retinol) from foods and supplements combined to no more than 1,600 RE (8,000 IU) per day.

Retinoids are compounds that are chemically similar to vitamin A. Over the past 15 years, synthetic retinoids have been prescribed for acne, psoriasis, and other skin disorders³⁶. Isotretinoin (Roaccutane® or Accutane®) is considered an effective anti-acne therapy. At very high doses, however, it can be toxic, which is why this medication is usually saved for the most severe forms of acne³⁷. The most serious consequence of this medication is birth defects.

It is extremely important for sexually active females who may become pregnant and who take these medications to use an effective method of birth control. Women of childbearing age who take these medications are advised to undergo monthly pregnancy tests to make sure they are not pregnant.

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